The Biology of Colon Cancer is program remains focused on fundamental cellular and molecular mechanisms of intestinal cell maturation and lineage specific differentiation, and how this establishes and maintains homeostasis of the intestinal mucosa; genetic and environmental factors, and their interactions, that perturb these processes and alter probability of tumor formation and progression; and approaches to prevent tumorigenesis and treat intestinal cancer. Members utilize novel cell systems in culture, mouse genetic models, and human tissues and subjects in their investigations. All of the members are independently funded by grants that are highly cancer focused, and most participate in large multidisciplinary programs that are jointly funded. During the last funding period, this included an NCI U01 Director's Challenge grant on molecular markers of relative drug sensitivity in colon cancer, and subsequently an NCI U54 Center grant on nutritional-genetic interactions in intestinal cancer. This joint funding, and a large number of joint publications, reflects the extensive interactions and collaborations among members of the Program. Moreover, members of the Program collaborate widely across the AECC and have made unique resources available to other Center members. The Program has continued to grow during the last 5 years, both by promotion from within and recruitment, made possible by support from the AECC and a pilot project program funded by the U54 Center grant. Leonard Augenlicht remains the Leader of this Program. There are currently 12 program members from 8 departments, of whom 11 are primary members, supported by 15 NCI ($3.7M Direct) and 2 other NIH grants. Five members are new to the program. Since the last CCSG review there have been 105 cancer-relevant research papers by members of this program of which 34% represent intraprogrammatic, and 33% represent interprogrammatic publications.